Adjuvant chemotherapy significantly reduces mortality in stage III colon cancer, however it is only marginally effective in the full population of stage II colon cancer patients [1]. While oncologists may recommend chemotherapy for some patients with additional poor prognosis factors, such as involvement of the visceral peritoneum or poorly differentiated histology, a guideline from the American Society of Clinical Oncology states that “direct evidence from randomized controlled trials does not support routine use of adjuvant chemotherapy for patients with stage II colon cancer” [2].
Although the ultimate goal is a test that predicts the level of effectiveness of chemotherapy, until that goal is reached, a test that stratifies patients by prognosis may guide the choice of treatment. A prognostic test may identify patients at a very low risk of recurrence, for whom chemotherapy is unwarranted; or it may identify other patients at such a high risk of dying from cancer that chemotherapy is prudent.
Several research groups have published prognostic tests for stage II colon cancer disease based on the expression levels of specific genes [3-6]. The most thoroughly validated test is Oncotype DX Colon™ (Genomic Health, Redwood City, Calif.). Using mRNA measurements of 7 target genes, and 5 reference genes, a recurrence score (RS) is derived that, in one study [6], partitions patients into three groups with three-year expected survival percentages of 88%, 82% and 78%, for the low risk, intermediate risk and high risk groups. In the same study, the treatment benefit score (TS), which is based on the expression levels of 6 other genes, was hypothesized to identify patients who will benefit from chemotherapy; however, TS failed to be statistically significant as a predictor of treatment benefit.
The advent of microarrays and molecular genomics has the potential for a significant impact on the diagnostic capability and prognostic classification of disease, which may aid in the prediction of the response of an individual patient to a defined therapeutic regimen. Microarrays provide for the analysis of large amounts of genetic information, thereby providing a genetic fingerprint of an individual. There is much enthusiasm that this technology will ultimately provide the necessary tools for custom-made drug treatment regimens. Currently, healthcare professionals have few mechanisms to help them identify cancer patients who will benefit from chemotherapeutic agents. Identification of the optimal first-line drug has been difficult because methods are not available for accurately predicting which drug treatment would be the most effective for a particular cancer's physiology. This deficiency results in relatively poor single agent response rates and increased cancer morbidity and death. Furthermore, patients often needlessly undergo ineffective, toxic drug therapy.
A need continues to exist in the medical arts, particularly in the area of oncology, for a tool useful in identifying and stratifying colon cancer patients into a group that would most benefit from an aggressive treatment regimen apart from the patients that would not likely benefit from an aggressive post-surgical chemotherapy treatment. Such would greatly enhance the quality of life of the colon cancer patient as well as provide a greater likelihood of patient therapeutic benefit from a selected course of treatment. In particular, methods are needed to identify those stage II colon cancer patients who are at a sufficiently high risk for relapse that they may benefit from chemotherapy. The treatment of colon cancer would be significantly advanced by a diagnostic test that identifies those stage II colon cancer patients whose risk of relapse is significantly decreased by adjuvant chemotherapy.